Anaplastic Thyroid Cancer

Rapid assessment, clinical trials could improve patient outcomes

BY Bryan Tutt

Left: A pretreatment computed tomography scan shows a large anaplastic
tumor (arrows) involving the left side of the thyroid gland. Right: A
computed tomography scan of the same patient 18 months after surgery,
chemotherapy, and radiation therapy shows no evidence of recurrence.
Images courtesy of Dr. G. Brandon Gunn.

Anaplastic thyroid cancer is extremely aggressive—only 20% of patients survive 1 year after their diagnosis—so patients require immediate assessment and treatment. A program at The University of Texas MD Anderson Cancer Center expedites the care of patients with this difficult-to-treat disease so that they can receive the best treatment possible, including access to clinical trials of promising new therapies.

Patients with anaplastic thyroid cancer typically present with advanced and symptomatic disease. In fact, all anaplastic thyroid cancers are considered stage IV disease, according to the AJCC Cancer Staging Manual, seventh edition. “Anaplastic thyroid cancer is difficult to manage because most patients typically are very ill and present with very large neck masses that compress the trachea,” said Maria E. Cabanillas, M.D., an associate professor in the Department of Endocrine Neoplasia and Hormonal Disorders.

Although anaplastic thyroid cancer represents only 1% of thyroid cancers, its aggressive nature warrants awareness. “Any rapidly growing lower neck mass should raise suspicion for anaplastic thyroid cancer,” said G. Brandon Gunn, M.D., an associate professor in the Department of Radiation Oncology. “I would encourage the referral of such patients to a tertiary care center for urgent evaluation.”

“These tumors grow very fast, so the intervention also needs to be very fast,” Dr. Cabanillas said. “The major challenge in anaplastic thyroid cancer is getting the patients seen quickly by a specialist for anaplastic thyroid cancer before they become very sick, preventing them from receiving any therapy.”

Rapid access

To make sure patients with anaplastic thyroid cancer receive timely attention, Dr. Cabanillas and her colleagues—notably Stephen Lai, M.D., Ph.D., an associate professor in the Department of Head and Neck Surgery—initiated a program called Facilitating Anaplastic Thyroid Cancer Specialized Treatment (FAST). Initiated in 2014, the FAST program coordinates with administrative and clinical staff to ensure that patients with anaplastic thyroid cancer are identified and given rapid access to care.

“In developing the program, we worked with the administrative staff to make sure they understood the urgency of getting these patients in to be seen,” Dr. Cabanillas said. “We also made sure the administrative staff knew all the synonyms for anaplastic thyroid cancer—squamous cell carcinoma of the thyroid, sarcoma of the thyroid, giant cell thyroid cancer, and others—so that patients referred to us with these diagnoses were identified as having anaplastic thyroid cancer.”

Once identified, patients with anaplastic thyroid cancer are given top priority. The FAST program initiated an arrangement for physicians with expertise in treating anaplastic thyroid cancer to keep open slots in their clinic schedule that are specifically reserved for new patients with the disease. “These patients need to see a lot of physicians—an endocrinologist, a head and neck medical oncologist, a head and neck radiation oncologist, a head and neck surgeon, and a palliative care specialist,” Dr. Cabanillas said.

Specialists such as Charles Lu, M.D., a professor in the Department of Thoracic/Head and Neck Medical Oncology, understood the importance of the program at its outset and were eager to participate. “We’re focusing on rapid assessment to get these patients in to see a doctor within a couple of days because many of these patients have a lot of symptoms,” Dr. Lu said.

So far, the program has been successful. The average referral-to-disposition time (the time from when the patient contacts MD Anderson to the time the first appointment is scheduled) for patients with anaplastic thyroid cancer is now half a day, and in fact the first available appointment is often too soon for patients who have to travel long distances. Dr. Cabanillas said, “We get patients in to see all of these anaplastic thyroid cancer specialists within a week of their first appointment, so patients have a treatment plan that can be initiated the second week they’re here.”

Challenges to diagnosis and treatment

In addition to patients’ advanced disease stage, other factors complicate the management of anaplastic thyroid cancer.

“The pathologic diagnosis of anaplastic thyroid cancer is difficult to make,” Dr. Cabanillas said, adding that tumors may contain spindle cells, giant cells, and/or squamous cells. “So we think it’s very important for any patient with a tumor suspected to be anaplastic thyroid cancer to have the diagnosis confirmed by an expert thyroid cancer pathologist because the diagnosis makes a difference in the patient’s treatment.”

For differentiated thyroid cancer, the most common type of thyroid cancer, the mainstay of treatment is surgery. “But patients with anaplastic thyroid cancer commonly present with advanced tumors that are not amenable to surgery,” Dr. Gunn said.

Another challenge in the treatment of anaplastic thyroid cancer is that the chemotherapy drugs used—taxanes and/or platinum drugs—are not very effective. “With standard chemotherapy agents, the tumor shrinkage rates for anaplastic thyroid cancer are low, and the duration of response tends to be short,” Dr. Lu said.

Radiation, therefore, plays a central role in the treatment of anaplastic thyroid cancer, either to achieve local tumor control or for palliation. According to Dr. Gunn, intensity-modulated radiation therapy (IMRT) is the standard modality used in such treatment. IMRT is often used in conjunction with radiosensitizing chemotherapy agents.

Standard therapy

Stage IVA anaplastic thyroid cancers (T4a, any N, M0), which are considered resectable, are typically treated with surgery followed by IMRT with radiosensitizing chemotherapy agents such as paclitaxel. Unfortunately, the disease tends to recur within 7 months.

Stage IVB cancers (T4b, any N, M0), which are confined to the neck but cannot be removed surgically, are treated using IMRT with radiosensitizing chemotherapy agents for local tumor control or for palliation. “We do the best we can to control the tumor in the neck—because it is so symptomatic, affecting breathing and swallowing—with chemotherapy,” Dr. Lu said. “But we will be the first to acknowledge that it’s not highly successful.” Occasionally, however, the combination of chemotherapy and radiation can shrink the tumor enough that surgery can be considered.

Stage IVC anaplastic thyroid cancer (any T, any N, M1) has no effective standard treatment. In such cases, chemotherapy or targeted therapy is usually the first treatment, to slow the growth of the metastases; and IMRT, with or without chemotherapy, may be used on the primary tumor for palliation. “The problem is that if we don’t address the tumor in the neck with radiation, the patient may asphyxiate,” Dr. Cabanillas said.

Recognizing the need for new treatments, MD Anderson physicians encourage their patients with anaplastic thyroid cancer to participate in clinical trials when possible. One such study, a multicenter clinical trial (RTOG0912), is currently enrolling patients with anaplastic thyroid cancer. “The study is investigating whether adding targeted therapy to standard chemoradiation can improve patient outcomes,” said Dr. Gunn, the principal investigator for the trial’s MD Anderson site.

Patients in the study receive a standard regimen for anaplastic thyroid cancer—IMRT and paclitaxel—and are randomly assigned to receive a placebo or the experimental drug pazopanib. Pazopanib is an antiangiogenic tyrosine kinase inhibitor approved for the treatment of advanced renal cell carcinoma and soft tissue sarcoma.

Although interim results are not yet available, the multicenter trial has already been successful in proving that it is possible to recruit enough patients with this rare disease for a trial. “This is encouraging to patients and investigators,” Dr. Gunn said.

In addition, patients with anaplastic thyroid cancer may be eligible for clinical trials of targeted agents that are open to patients with any solid tumor that has a specific genetic mutation. “Because the prognosis is so poor, we immediately request molecular profiling for any patient with anaplastic thyroid cancer rather than wait to see how the patient does with standard treatment,” Dr. Lu said. “Less than half of patients with anaplastic thyroid cancer have targetable mutations, but those who do may benefit from targeted agents in a clinical trial.”

For example, BRAF mutations are seen in 25% of anaplastic thyroid tumors, so Drs. Lu and Cabanillas and their colleagues refer patients with such mutations to a clinical trial or off-label treatment with dabrafenib, which inhibits the BRAF kinase, plus trametinib, which inhibits the MEK kinase along the same signaling pathway. “We’ve had some promising results so far,” Dr. Cabanillas said.

In addition to the ongoing studies, more clinical trials are being planned for patients with stage IVB and IVC anaplastic thyroid cancer. For example, patients without a targetable mutation will be offered lenvatinib, a multiple kinase inhibitor, in a clinical trial scheduled to open in the next few months. Also opening soon is a trial to test neoadjuvant systemic therapies that boost the immune system or target a specific genetic mutation. Depending on the response to neoadjuvant therapy, the patients’ thyroid tumors will be treated with surgery followed by IMRT or with IMRT only.

“Five years ago, we had nothing to offer other than the standard of care for patients with anaplastic thyroid cancer. We now have some very promising studies,” Dr. Cabanillas said. “We are trying to improve the standard of care for anaplastic thyroid cancer.”